Enteroviruses
Author: Yin Huang
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General overview
Enterovirus, a kind of small (30 nm), nonenveloped, single-stranded RNA viruses, belongs to the family Picornaviridae. While most of the enterovirus infections are relatively mild and result in complete recovery of the patient, they can also cause severe and fatal diseases such as meningitis, encephalitis, myocarditis, neonatal sepsis, and polio. Infection occurs mainly via fecal-oral transmission and less commonly by respiratory droplets. While no known non-human reservoirs have been identified, water-borne, foodborne, and blood-borne transmissions have been reported (Stalkup and Chilukuri 2002).
Summary Data
Cliver (1981) challenged pigs with Porcine enterovirus type 3 and 7 via oral exposure route.
Table 3.1. Summary of the enterovirus data and best fits
Experiment number |
Reference |
Host type/pathogen strain |
Route/number of doses |
Dose units |
Response |
Best-fit modela |
Optimized parameters |
ID50
|
1 |
Cliver, 1981 |
pigs/ Porcine enterovirus type 3 |
oral/3 |
pfu |
infection |
Exponential |
k = 2.96E-04 |
2340.15
|
2* |
Cliver, 1981 |
pigs/ Porcine enterovirus type 7 |
oral/3 |
pfu |
infection |
Exponential |
k = 3.75E-03 |
185.10
|
|
Experiment serial number |
Reference |
Host type |
Agent strain |
Route |
# of doses |
Dose units |
Response |
Best fit model |
Optimized parameter(s) |
LD50/ID50
|
63* |
[1] |
pig |
porcine, PE7-05i |
oral |
3 |
pfu |
infection |
exponential |
k = 3.74E-03 |
1.85E+02
|
62 |
[1] |
pig |
porcine, PE3-ECPO-6 |
oral |
3 |
pfu |
infection |
exponential |
k = 2.96E-04 |
2.34E+03
|
*This model is preferred in most circumstances. However, consider all available models to decide which one is most appropriate for your analysis.
|
|
*Recommended Model
It is recommended that experiment 1 should be used as the best dose-response model. A more virulent strain in experiment 1 can be more meaningful for emergency preparedness.
a:
Optimization Output for experiment 63
pigs/ Porcine enterovirus type 7 [1]
Dose |
infected |
Non-infected |
Total
|
250 |
4 |
2 |
6
|
250 |
3 |
3 |
6
|
1000 |
5 |
0 |
5
|
|
Goodness of fit and model selection
Model |
Deviance |
Δ |
Degrees of freedom |
χ20.95,1 p-value |
χ20.95,m-k p-value
|
Exponential
|
0.614
|
-5.49e-05
|
2
|
3.84 1
|
5.99 0.736
|
Beta Poisson
|
0.614
|
1
|
3.84 0.433
|
Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.
|
|
Optimized k parameter for the exponential model, from 10000 bootstrap iterations
Parameter
|
MLE estimate
|
Percentiles
|
0.5% |
2.5% |
5% |
95% |
97.5% |
99.5%
|
k |
3.74E-03 |
1.83E-03 |
2.19E-03 |
2.19E-03 |
5.62E-03 |
5.62E-03 |
5.62E-03
|
ID50/LD50/ETC* |
1.85E+02 |
1.23E+02 |
1.23E+02 |
1.23E+02 |
3.16E+02 |
3.16E+02 |
3.79E+02
|
*Not a parameter of the exponential model; however, it facilitates comparison with other models.
|
|
Parameter histogram for exponential model (uncertainty of the parameter)
Exponential model plot, with confidence bounds around optimized model
Optimization Output for experiment 62
Pigs/ Porcine enterovirus type 3 Strain model data [1]
Dose |
infected |
Non-infected |
Total
|
100 |
0 |
3 |
3
|
250 |
0 |
6 |
6
|
1000 |
2 |
4 |
6
|
|
Goodness of fit and model selection
Model |
Deviance |
Δ |
Degrees of freedom |
χ20.95,1 p-value |
χ20.95,m-k p-value
|
Exponential
|
1.24
|
-0.000314
|
2
|
3.84 1
|
5.99 0.537
|
Beta Poisson
|
1.24
|
1
|
3.84 0.265
|
Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.
|
|
Optimized k parameter for the exponential model, from 10000 bootstrap iterations
Parameter
|
MLE estimate
|
Percentiles
|
0.5% |
2.5% |
5% |
95% |
97.5% |
99.5%
|
k |
2.96E-04 |
2.40E-17 |
2.40E-17 |
2.40E-17 |
7.19E-04 |
7.19E-04 |
1.02E-03
|
ID50/LD50/ETC* |
2.34E+03 |
6.77E+02 |
9.64E+02 |
9.64E+02 |
2.89E+16 |
2.89E+16 |
2.89E+16
|
*Not a parameter of the exponential model; however, it facilitates comparison with other models.
|
|
Parameter histogram for exponential model (uncertainty of the parameter)
Exponential model plot, with confidence bounds around optimized model
Optimized Models and Fitting Analyses
Optimization Output for experiment 1
Table 3.3: Goodness of fit and model selection
Model |
Deviance |
Δ |
Degrees of Freedom |
χ20.95,1 p-value |
χ20.95,m-k p-value
|
Exponential
|
1.24
|
3.00E-04
|
2
|
3.84 0.986
|
5.99 0.537
|
Beta Poisson
|
1.24
|
1
|
3.84 0.265
|
Exponential is best fitting model
|
|
|
Figure 3.1 Parameter histogram for exponential model (uncertainty of the parameter)
Figure 3.2 Exponential model plot, with confidence bounds around optimized model
Optimization Output for experiment 2
Table 3.6: Goodness of fit and model selection
Model |
Deviance |
Δ |
Degrees of Freedom |
χ20.95,1 p-value |
χ20.95,m-k p-value
|
Exponential
|
0.61
|
1.00E-04
|
2
|
3.84 0.994
|
5.99 0.736
|
Beta Poisson
|
0.61
|
1
|
3.84 0.433
|
Exponential is best fitting model
|
|
|
Figure 3.3 Parameter histogram for exponential model (uncertainty of the parameter)
Figure 3.4 Exponential model plot, with confidence bounds around optimized model
Summary
The different LD50 for these two experiments indicates various virulence between pathogen strains.
References
Cliver, D. O. (1981). "Experimental infection by waterborne enteroviruses." Journal of Food Protection 44: 861-865.
Stalkup, J. R. and S. Chilukuri (2002). "
Enterovirus infections: a review of clinical presentation, diagnosis, and treatment." Dermatologic clinics
20(2): 217-223.
- ↑ 1.0 1.1 1.2 1.3 Cliver, D. O. (1981). "Experimental infection by waterborne enteroviruses." Journal of Food Protection 44: 861-865.